The relationship between infused synthetic bovine PTH-(1-34) and plasma concentrations of minerals and vitamin D metabolites was studied in eight calves (150-230 kg) and two thyroparathyroidectomized goats. Calves were infused iv with saline for 15-20 h. Then, calves were infused with one of three types of solution for an additional 35-h period. Three of the eight calves received 3 ng/kg X min (group H), three received 0.75 ng/kg X min (group L), and the remaining two calves received control saline over a 33-h period (group C). Blood samples were taken every 4-6 h. Plasma calcium, phosphorus, hydroxyproline, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] remained relatively constant in control calves. PTH infusions into calves in group H resulted in an increase in plasma calcium from 2.4 to a plateau of 3.0 mmol/liter. PTH infusion caused no change in plasma phosphorus, but increased urinary excretion of phosphorus. Infusion of PTH caused a moderate increase in urinary calcium excretion, followed by pronounced calciuria after PTH withdrawal. Plasma concentrations of 1,25-(OH)2D decreased from about 30 pg/ml at the start of infusion to undetectable levels (less than 5 pg/ml) at the end of the infusion and for 30 h thereafter. Similar, but less pronounced, changes in plasma calcium and 1,25-(OH)2D concentration were observed in group L. Hypocalcemia and hypophosphatemia developed in the two lactating goats after thyroparathyroidectomy, and plasma 1,25-(OH)2D concentrations were decreased. PTH infusion (3 ng/kg X min) corrected the hypocalcemia and hypophosphatemia and markedly raised plasma 1,25-(OH)2D concentrations. When calcium chloride was infused in addition to PTH, the resulting hypercalcemia (3 mmol/liter) was associated with a marked reduction in plasma 1,25-(OH)2D. We conclude that the concentration of calcium in plasma has the major regulatory role on plasma 1,25-(OH)2D concentrations in ruminant species when potentially conflicting signals, such as hypercalcemia and high PTH concentrations, are present simultaneously.